Our protective armor, skin, is the largest organ in the body. But armor only, skin is not. This highly dynamic network of cells, nerves, and blood vessels serves the body in diverse ways.

Clearly, skin's protective function is paramount, providing internal organs and tissues with a physical barrier from the environment and the dangers therein: toxins, heat and cold, and disease-carrying microbes. But skin also plays an important role in preserving fluid balance and in regulating body temperature and sensation. Nerves buried deep within skin allow us to sense the presence of potentially harmful invaders, such as bees. Immune cells resident in skin help the body prevent and fight disease.

For these reasons, the loss of skin due to burns or trauma can deal the body a severe blow, impairing or even eliminating the many vital functions this organ performs.

Burns
Each year in the United States, 1.1 million burn injuries demand medical attention. Ten thousand people die every year of burn-related infections. Tragically, many burn victims are children. The good news is that, in recent years, survival statistics for serious burns have improved dramatically. Twenty years ago, for instance, burns covering half the body were routinely fatal. Today, patients with burns encompassing 90 percent of their body surface can survive, albeit sometimes with permanent impairments.

By funding basic research aimed at understanding how the body, especially skin, responds to burn- and trauma-related injury, the National Institute of General Medical Sciences (NIGMS) has played an important role in driving burn injury survival statistics upward. Among the advances that have contributed directly to this public health benefit are discoveries of the importance of proper wound care, adequate nutrition, and infection control. NIGMS-funded research has also led to the development of widely used commercially available skin-replacement products for the treatment of injury caused by severe burns.

Burn-induced skin loss affords bacteria and other microorganisms easy access to the warm, moist, nutrient-rich fluids that course through the body, while at the same time it provides a conduit for the rapid and dangerous loss of these fluids. Extensive blood loss can thrust a burn or trauma victim into shock, a life-threatening condition in which blood pressure plunges so low that vital organs--such as the brain, heart, and kidneys--simply cannot get enough blood (and thereby oxygen) to function. Hence, replenishing skin lost to severe burns is an urgent matter in the care of a burn patient. When a patient has lost 80 or 90 percent of the skin as a result of direct contact with scalding hot liquids, flames, harsh chemicals, electrical current, or nuclear radiation, two immediate tasks come to the fore. First, a burn surgeon must surgically remove the burned skin, then the unprotected underlying tissue must be quickly covered. Two classes of biomaterials useful in covering the wound are laboratory-grown skin cells and artificial skin; the two are sometimes used in combination.

Laboratory-Grown Skin Cells
In the mid-1980s, with a grant from NIGMS, Dr. Howard Green of Harvard Medical School conceived a method for growing a type of human skin cells called keratinocytes (which populate skin's upper, or epidermal, layer) outside of the body. Dr. Green's keratinocyte culture research paved the way for the method to proceed to commercialization.

Growing cells in a laboratory, a technique called "culturing," can be a tricky business. No general recipe exists: Every different cell type in the body requires a unique set of conditions, and some simply will not grow this way at all. The secret to Dr. Green's technique, in which he "seeded" human keratinocytes onto a layer of mouse-derived fibroblast (connective tissue) cells in a plastic culture dish, is derived from Mother Nature herself. Presumably, the technique works because it mimics what happens in actual skin, whose lower layer, called the dermis, is composed predominantly of fibroblasts. The principle function of fibroblasts is to produce proteins called collagen and elastin that provide structure to skin. To ensure that the keratinocytes, not the fibroblast "feeder" cells, would multiply in his culture flask, Dr. Green first irradiated the fibroblasts so they would not continue to divide but would still pump out nutrients into the culture broth. After several days in such an environment, the few starting keratinocytes grew into a sheet of epidermal-like tissue.

The product that eventually resulted from Dr. Green's work, called Epicelo, is currently licensed by a company called Genzyme Tissue Repair (Cambridge, Massachusetts). Epicelo is used to treat deep wounds that require grafting (skin replacement), such as occurs with severe burns. However, since Epicelo replaces the lost epidermal layer only, it works best in combination with something that restores the dermal layer of skin. Epicelo is not an artificial skin, but rather a method in which new epidermis is "grown to order" in a laboratory from surgically harvested skin cells taken from an unburned area of the patient. Products like Epicelo are termed "autologous" grafts, meaning that the source of the epidermal graft material is taken from skin of the same patient who receives it. (In contrast, the source of skin for an "allograft" is skin from another person, sometimes even a cadaver. Allografts offer only temporary cover, as they are quickly rejected by the patient's immune system.)

Source: National Institute of General Medical Sciences
Reviewed: February 2002

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